Emboli not the only risk to the brain following carotid stenting

4th May 2006

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Although the debate is still ranging as to whether embolic protection systems do provide any benefit when used in conjunction with carotid artery stenting, in an absorbing presentation, Sumaira MacDonald, Newcastle, UK, said that embolic injury is not the only risk to the brain.

She began by stating that there is a widespread belief that the primary cause of neurological injury during and immediately after carotid stenting is cerebral embolization and, as a result, the focus of both clinicians and industry has been on methods to reduce this risk. However, MacDonald pointed out that other causes of peri-procedural neurological injury have largely been overlooked, perhaps because they are so poorly understood.

For instance, serum changes in biochemical markers of neurological damage including neuron specific enolase (neuronal injury) and S100B (glial injury) were analyzed in 30 patients undergoing carotid stenting within a randomized trial comparing protected and unprotected stenting. Samples were taken from the ipsilateral jugular vein pre-stenting, and at one, six and 24 hours post-stenting. There was a significant and group-independent rise in S100B (p<0.0005) that did not correlate with other markers of cerebral embolization. This is evidence of glial injury independent of embolization. "As glial elements contribute to the integrity of the blood brain barrier, the rise in S100B implies transient loss of blood brain barrier function as a result of hemodynamic injury", MacDonald said.
However, hyperperfusion syndrome is a distinct clinical entity that occurs in less than 1% of patients after stenting. However, procedural (<24 hours) hypotension, defined as a reduction in systolic blood pressure of greater than 30 mmHg below pre-stenting values, may occur in up to 76% of patients after carotid stenting despite routine atropine administration.
A review of more than 400 endovascular carotid procedures demonstrated that patients with hemodynamic instability had an increased likelihood of procedural stroke (odds ratio [OR] 2.6; 95% CI 1.2-5.9), myocardial infarction (OR 4.5; 95% CI 1.2-16.9) and death (OR 3.6; 95% CI 1.0-7.6]. MacDonald revealed that hemodynamic instability is therefore common and clinically relevant.
Hypotension, if sufficiently severe, may cause watershed infarction. Lesser degrees of hypotension may render an otherwise inconsequential microembolic shower very relevant owing to impaired washout. She also claimed that hypotension may limit appropriate collateral flow to an ischemic territory, “Such hemodynamic instability is clearly detrimental to those with severe coronary artery disease and, last but not least, hypotensive responses may be a surrogate marker of high-risk patients with generalized atherosclerosis and decreased arterial compliance.”
Overall, MacDonald said “Stroke after carotid stenting is assumed to be embolic. If, however, we scrutinise the available Level I evidence supporting stenting (in trials against carotid endarterectomy) on the basis that these are robust independently-reviewed data analysed off-site, it is evident that we do not know how many of the ischemic strokes are truly embolic and likely to be in the middle cerebral artery territory and how many are watershed, implying an hemodynamic aetiology. There is a lack of reporting clarity despite cross-sectional imaging of brain”.
Furthermore, the procedural microembolisation rate (on transcranial Doppler) and the new white lesion rate on diffusion-weighted MRI correlate poorly with cognitive and overt neurological deficit. The embolic stroke-rate for series and registries of carotid stenting has fallen steadily and the cause is multi-factorial. The abundant macro-embolic debris collected in early reports of first-generation protection devices is not routinely encountered in current clinical practice, largely because of technical refinements.
Therefore, MacDonald concluded that in order to further refine the safety profile of carotid stenting, causes of procedural stroke other than embolisation must be considered and the practical significance of intra- and post-procedural hemodynamic instability addressed by judicious control of periprocedural hemodynamics.